Applying Innovative Solutions to Canada’s Orphan Product Access Strategy

Mark Krueger, MPH 8 November 2016

Presentation goals

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Consider innovative

solutions to rare disease treatment access outside of

Canada

Discuss key learnings

Examine potential implications for Canada’s rare

disease patients and families

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Introducing MK&A

Who we are

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MK&A (Mark Krueger & Associates, Inc.) is a specialized health care constituency relations firm offering targeted services to

pharmaceutical, biotech, device and diagnostic companies

Experience Our expertise includes multiple

therapeutic areas and our associates have varied

backgrounds in both industry and advocacy sectors,

representing a wide-breadth of functions.

Networks Our relationships span a wide range of groups that influence

a product’s success and company reputation including patient advocates, consumer

and professional thought leaders, payers and

policy makers.

Knowledge We provide strategic

thinking and counseling, and understand the medicine and science behind our

clients’ products.

Experience with HTA and pricing

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Innovative approaches to orphan product access

Challenges create an unsustainable business model

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Drivers Implications •  Successful basic and clinical

research •  Availability of costly and effective

targeted therapies for small populations

•  Economic and demographic pressures on health care budgets

•  Focus on ensuring robust orphan drug development and access

•  Blockbuster orphan drugs and increasingly high prices for many compounds

•  Erosion of support for enabling legislation and regulation

•  Investors’ expectations •  Responsibility to provide reasonable return

•  Short-term gain •  Longer-term view

Disparate views of the way ahead

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Looking for a “one size fits all” solution

QALY can never meet demands of orphan drugs by definition

Social benefit and value definitions do not fit

Canada: At an inflection point

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Optimal care in sight

Recognition of need for new options

Opportunity to learn from and adapt external

solutions

Examining international solutions to orphan product access challenges: United States

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Key developments the United States

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Natural history studies and patient registries

New approval pathways

Value demonstration

NORD-FDA Natural History Study Project

•  NORD, FDA and patient groups to document natural history of 19 rare diseases •  Data show how diseases develop and progress, and impact of therapeutic

interventions •  Registries utilize NIH/OPD best practices, scientific and medical experts,

and FDA guidance on instrument design

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Application to orphan drugs •  Disease specific patient-centered

registries used to gain better understanding of rare diseases

•  Registries will allow patients from around the world to share relevant data; useful method of aggregating small population data

•  Collaboration will result in registry best practice toolkits and templates for patient groups to use

Breakthrough therapy designation

•  Early evidence must show substantial benefit over existing therapies for serious condition

•  Data on early evidence must be clinical •  Provides intensive FDA guidance throughout development process

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Approval time Application to orphan drugs

•  Treatments often include orphan drugs

•  Measurement of relative effectiveness; if few treatments exist, may aid approval of orphan products

•  27 out of 47 designations given to orphan products since inception of program

Accelerated approval

•  Early evidence must show substantial benefit over existing therapies for a serious condition

•  May use surrogate endpoints to demonstrate clinical benefit •  Approval granted on conditional basis. Sponsor must conduct post-approval trials

to confirm benefits.

Adapted from Genentech’s “Guide to FDA Approval Designations” 14

Application to orphan drugs

•  Measurement of surrogate endpoints may aid approval of orphan products

•  Assessment accept limited amount of data, often the case in rare diseases

•  Serepta’s Exondys 51TM (eteplirsen) most recently benefitted from this process

Value demonstration

•  Funds comparative clinical effectiveness research to improve quality of evidence available, including in rare diseases

•  Helps determine which healthcare option available best under given circumstances

•  Input welcome from across rare disease community to inform best evaluation of orphan treatments

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•  Evaluates evidence on value of medical tests, treatments and delivery system innovations

•  Performs analyses on effectiveness and costs, and develops reports to aid in decision making

Patient-Centered Outcomes Research Institute (PCORI)

Institute for Clinical and Economic Review (ICER)

Challengers to access

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"Exondys 51 failed to show it improves health outcomes, and therefore it is not

a covered benefit for our members"

Leslie Porras, spokeswoman for

FDA grants accelerated approval to first drug for Duchenne muscular dystrophy

Examining international solutions to orphan product access challenges: Europe

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Addressing challenges in Europe: Key developments

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Reference networks and registries

Priority medicines scheme

Adaptive pathways

Adaptive licensing

Coordinated access

Early scientific advice

European Reference Networks (ERN) and registries

•  Tackles challenge of scarcity of expertise in rare diseases and scattering of small patient populations across Europe

•  Creates governance structure for knowledge sharing and care coordination across EU; clinicians to work across borders

Adapted from http://www.eurordis.org/content/about-european-reference-networks 19

Application to orphan drugs •  Allows stakeholders in rare

diseases to make better decisions related to treatment and care of patient population

•  Over 24 separate ERNs touching rare diseases

Priority Medicines (PRIME scheme)

•  Builds on existing approval framework •  Offers early, proactive and enhanced scientific and regulatory

support •  Leads to accelerated assessment

Source: European Medicines Agency 20

Application to orphan drugs

•  Measurement of relative effectiveness; if few treatments exist, may aid approval of orphan products

•  Direct access to enhanced advice for scientific and regulatory guidance

Mechanisms of Adaptive Pathways to Patients (MAPPs)

•  New regulatory route of approval •  Iterative approach to bringing medicines to market through widening

indication or reduction of uncertainty •  Provides access to beneficial treatments to right patient groups at earliest

appropriate time

Adapted from ONXEO’s “Adaptive Pathways: An Update” presented at EUCOPE Meeting 20/09/16 21

Application to orphan drugs Targeted for specific products and populations:

Products intended to treat clearly defined subgroup of patients based on high unmet need

Adaptive Licensing

•  Pilot program launched in March 2014 •  Use after initial license closely monitored leading to full license with

decreasing levels of active surveillance •  Builds on existing processes, e.g., scientific advice, compassionate use,

patient registries and pharmacovigilance tools

Source: European Medicines Agency 22

Application to orphan drugs

•  Framework determines how or if compound holds sufficient promise to address unmet need

•  Allows for early authorization of medicine in restricted patient population to start

•  “Balances timely access for patients with the need to provide adequate evolving information on their benefits and risks” – Hans-George Eichler, EMA senior medical officer

Mechanism of Coordinated Access to Orphan Medicinal Products (MoCA)

•  Aims to coordinate and facilitate access by bringing stakeholders together

•  Nine pilots implemented by MEDEV since mid-2015 •  Tackles access to innovative precision products, e.g., gene therapy,

through cross-national collaboration

Adapted from EURORDIS’ “Call on Payers to Get Things Done” presented at ECRD 28/05/16 23

Application to orphan drugs •  Specifically targets orphan drug

development and approval processes: framework includes determination of number of patients

•  Defines and identifies added value of new orphan medicinal product through use of Transparent Value Framework or other means

•  Potential for prescribing improvements in Centres of Expertise which treat rare disease patients

Example of MoCA pilot

•  Early dialogue on targeted gene therapy for small population (~ 10,000 patients in Europe)

•  Complex therapy: 80 days minimum for all treatment steps plus six months of active follow-up

•  Need to build early understanding of significant endpoints to determine value of product

•  Almost impossible to create European network to serve all Member States; treatment limited to few Centers of Expertise

•  Implication: If all European patients to have access to treatment, this means

•  enabling genuine cross-border patient mobility •  obtaining administrative pre-authorizations for treatment •  securing national payers’ acceptance of need for and price of treatment

Adapted from EURORDIS’ “Call on Payers to Get Things Done” presented at ECRD 28/05/16 24

Shaping European Early Dialogues (SEED)

•  Reduces risk of producing inadequate data to support value proposition

•  Involves 14 HTA bodies from EUnetHTA organizations and industry

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Application to orphan drugs

•  Allows for inclusion of customization of dialogue and review to reflect sponsor interests, e.g., orphan designation and choice of economic comparator

•  Takes into account clinical added benefit, cost-effectiveness and relative effectiveness

•  Involves EMA and COMP in discussion process

•  Directly addresses specific industry concerns on orphan drug rebates

EURORDIS’ proposal for “Table for Price Negotiation”

Reasoning •  Recognises national level not

appropriate for decisions on products for small patient populations ‒  Need collaborative approach

among Member States •  Enables informed and integrated

decision-making on value assessment, and real-world evidence generation

•  Addresses sustainability of medicines, improves patient access and accelerates market access

Adapted from EURORDIS’ “Call on Payers to Get Things Done” presented at ECRD 28/05/16 26

Description •  Enables European approach to

negotiating prices with pharmaceutical companies

•  Leads to more constructive decision-making on appropriate levels of pricing and reimbursement

•  Belgium, Luxembourg and Netherlands have taken first steps toward model; Austria, Italy and Portugal have expressed interest

Examining global solutions to orphan product access challenges

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Next steps in improving market access to orphan products

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Discovery Pre-clinical Clinical Approval Market

As stakeholders better integrate patient perspectives into R&D and regulatory decisions, patient inclusion

alone not enough to create appropriate market access

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Implications for Canada

Understanding the problem

Challenges: •  Limited resources •  Fragmented system •  HTA system not suitable for orphan products •  Patient participation not enough

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Goal: Sustainable access to orphan products in Canada

New HTA model trends

•  Designed to incentivize innovation •  Integrates value demonstration from earliest point •  Treatment-eligible populations start small with potential

to expand •  Registries generate real-life data for more informed

decision making •  Progressive reduction in uncertainty sought: “De-risk the entire lifecycle, not just the regulatory space.”

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Opportunity for consideration

Adapted from EURORDIS’ “Call on Payers to Get Things Done” presented at ECRD 28/05/16 32

Create a new model of patient access to guarantee better value for money and stronger sustainability for all

rather than access vs. sustainability

Access and sustainability

Requires tackling two main drivers:

Science §  Pre-requisite for orphan products; evidence

generation has to occur all along development continuum

§  Assessment of safety, efficacy/effectiveness for small populations requires post-market authorization research activities

§  Current system siloed and no longer suited to today’s scientific reality

Economy §  Industry and payers must agree upfront:

−  how to approach value (e.g. in situations of small populations and limited knowledge)

−  how to ensure more robust value assessment over time

−  how to better link value and price

Opportunities for Canada

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Promote transparency in processes

Demonstrate value across development and access continuum

Add flexibility within current regulatory frameworks, e.g. iterative approval

Create pan-Canadian approach for decisions on products for small patient populations, e.g. orphan drugs and precision medicine

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Thank you